Hydrochloric Acid → 4-(N-(furan-2-ylmethyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acid

HRID 1686206Notes

Reaction equation

HRID 1686206 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)[S:8]([C:11]1[CH:28]=[CH:27][C:14]([C:15]([O:17]CC2C=CC(OC)=CC=2)=[O:16])=[CH:13][CH:12]=1)(=[O:10])=[O:9].[Li+].[OH-].C1COCC1.CO.Cl>>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]([CH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[S:8]([C:11]1[CH:28]=[CH:27][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=1)(=[O:10])=[O:9]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 602089104-Methoxybenzyl 4-(N-(furan-2-ylmethyl)-N-(4-methoxybenzyl)sulfamoyl)benzoateHCID 86635511LiOH methanol THF

Product 1

HCID 238855044-(N-(furan-2-ylmethyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acidYield 36.5%

Procedure

4-Methoxybenzyl 4-(N-(furan-2-ylmethyl)-N-(4-methoxybenzyl)sulfamoyl)benzoate (Example 5-2a) (750 mg, 1.4 mmol) was stirred a 2/2/1 mixture of aqueous 2N LiOH/THF/MeOH (45 mL) at ambient temperature for 3 hours. The solution was acidified with aqueous 1N aq HCl to a pH of ˜3 (ca. 100 mL) and extracted with ethyl acetate (3×, 100 mL). The combined organic extracts were dried over sodium sulfate and concentrated on the rotovap. The residue was taken up in MeOH (9 mL) and purified by reverse phased HPLC (5-95% ACN in H2O gradient:40 minutes) in three-3 mL aliquots. The pure fractions were combined and concentrated to a white solid. The product was dissolved in absolute ethanol and evaporated (4×, 20 mL) to provide pure 4-(N-(furan-2-ylmethyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acid (205 mg, 36%) as a white solid. M.p. 151-152° C. 1H NMR (DMSO-d6, 400 MHz): 3.71 (s, 3H), 4.24 (s, 2H), 4.27 (s, 2H), 6.14 (d, 1H, J=3.2 Hz), 6.26 (m, 1H), 6.87 (d, 2H, J=9.2 Hz), 7.14 (d, 2H, J=8.8 Hz), 7.41 (s, 1H), 7.89 (d, 2H, J=8 Hz), 8.06 (d, 2H, J=8.4 Hz), 13.48 (bs, 1H). MS 400 (M−H).

Workup

  1. extractionextracted with ethyl acetate (3×, 100 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. concentrationconcentrated on the rotovap
  4. custompurified by reverse
  5. customHPLC (5-95% ACN in H2O gradient:40 minutes)
  6. concentrationconcentrated to a white solid
  7. dissolutionThe product was dissolved in absolute ethanol
  8. customevaporated (4×, 20 mL)

Sources & evidence

ORD record
ord-b819b9d49303455696c0b4bb597b24f0
Source dataset
uspto-grants-2012_04
Patent number
US08148544B2

Reaction notes

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